RMD Open最新文献

Objective: To assess the long-term effect of bimekizumab, a dual inhibitor of IL-17A and IL-17F, on patient-reported symptoms, function and health-related quality of life (HRQoL) in patients with axial spondyloarthritis (axSpA) from phase 3 studies and their open-label extension.

Methods: BE MOBILE 1 (non-radiographic-axSpA) and 2 (radiographic-axSpA) comprised 16-week double-blind placebo-controlled and 36-week maintenance periods. From week 16, all patients received subcutaneous bimekizumab 160 mg every 4 weeks. At week 52, eligible patients could enrol in the open-label extension BE MOVING and continue bimekizumab treatment. Spinal pain (rated on a numerical rating scale from 0 (no pain) to 10 (maximum pain)), morning stiffness (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) average of Q5/6), fatigue (BASDAI Q1; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale), sleep quality (Medical Outcomes Study (MOS) Sleep Scale Index II), physical function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and HRQoL (36-Item Short Form Survey (SF-36) physical component summary (PCS)/mental component summary (MCS); Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire) were reported to week 104.

Results: In total, 494/586 (84.3%) patients entered BE MOVING at week 52; 456 completed week 104. Patients reported substantial changes from baseline to week 104 in total spinal pain (-4.3), nocturnal spinal pain (-4.3), morning stiffness (-4.3) and fatigue (BASDAI Q1: -3.4; FACIT-Fatigue: +9.9). Over half reported total and nocturnal spinal pain scores ≤3 at week 104. Similar improvements to week 104 were shown in sleep (MOS-Sleep Scale: +10.2), physical function (BASFI: -2.9) and HRQoL (SF-36 PCS: +12.4; ASQoL: -5.6).

Conclusions: Bimekizumab treatment resulted in sustained improvements in patient-reported symptoms and their impacts across the full disease spectrum of axSpA over 2 years, underscoring its long-term potential for improving patients' daily lives.

Trial registration numbers: NCT03928704, NCT03928743, NCT04436640.

Objective: To investigate complement system activation and complement protein levels in relation to radiographic progression in axial spondyloarthritis (axSpA) within a longitudinal randomised controlled trial (RCT) of radiographic axSpA patients initiating tumour necrosis factor inhibitor (TNFi) therapy.

Methods: Serum samples from 96 patients with active radiographic axSpA in the multicentre RCT CONSUL were analysed by immunoassays for complement activation, that is, C3dg and complement proteins (MBL, CL-L1, M-, H- and L-ficolin; MASP-1,-2 and -3; and MAp44) before and after 108 weeks of TNF inhibitor therapy with golimumab.

Results: Baseline serum levels of total complement activation, that is, C3dg and lectin pathway activating protease MASP-1 were elevated in patients with new bone formation (new syndesmophytes and/or growth of existing syndesmophytes) after 2 years of follow-up, whereas baseline MASP-3 levels were decreased. Assessed by univariate logistic regression, baseline levels of MASP-1, MASP-3 and C3dg were associated with the development of new bone formation and remained significant in a corresponding multivariate logistic regression analysis. At follow-up, serum levels of C3dg and complement lectin pathway initiator L-ficolin were elevated in patients with new bone formation, and C3dg remained significant in a corresponding multivariate logistic regression analysis.

Conclusions: Complement activation marker C3dg, MASP-1 and MASP-3 levels before TNFi therapy predicted new bone formation after 2 years of follow-up among axSpA patients with a high risk of radiographic progression. Furthermore, levels of L-ficolin and C3dg at follow-up were elevated in axSpA patients with new bone formation. Our findings support an association between activation of the complement system and radiographic spinal progression in patients with axSpA.

Objectives: Activated synovial fibroblasts play a key role in rheumatoid arthritis (RA). Positron emission tomography-CT (PET-CT) using ^68gallium-labelled fibroblast activation protein inhibitor (FAPI) allows the detection of FAP-expressing activated fibroblasts in humans in vivo. Herein, this study aimed to investigate whether fibroblast activation already occurs in the pre-clinical phase of RA and whether it is associated with the development of clinical disease.

Methods: ⁶⁸Ga-FAPI-46 PET-CT was performed in individuals positive for anti-citrullinated protein antibodies (ACPAs) with clinically suspect arthralgia without present or past signs of joint swelling or present or past anti-rheumatic therapy. All participants underwent structured clinical and laboratory evaluations and were followed for the development of RA. Synovial FAPI uptake was quantified and related to demographic characteristics, joint tenderness, ACPA levels and RA development.

Findings: Eighteen RA-at-risk individuals (male/female: 7/11; mean age, 47 (SD 14) years) underwent ⁶⁸Ga-FAPI-46 PET-CT and were followed for a median of 42 weeks. Five participants (28%) developed RA with a median of 12 weeks (IQR, 11-20), whereas 13 remained disease-free. Total lesion FAPI-uptake (TL-FAPI) was a significant predictor of RA development (HR 4.58, 95% CI 1.38 to 15.22, p=0.013). Increasing TL-FAPI at the joint level was also associated with tenderness (isk ratio 1.14, 95% CI 1.08 to 1.22, p=0.001).

Conclusions: The findings in this small RA-at-risk cohort suggest that synovial fibroblast activation occurs early in the disease process of RA and is associated with an increased risk for clinical RA onset. These results warrant further research on FAPI-PET-CT to improve risk assessment for clinical RA onset.

Objectives: To identify in a genetically susceptible population individuals at higher risk of developing rheumatoid arthritis (RA) using a classification approach combining known epidemiological risk factors, serological biomarkers, genetics, clinical signs and symptoms.

Methods: We used data from the prospective SCREEN-RA (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) cohort of 1540 first-degree relatives of RA patients (RA-FDRs). The primary outcome was the development of RA. Additionally, we used seropositive inflammatory arthritis (IA) as a secondary outcome for exploratory analyses. Balanced random forest (BRF) models were fit and evaluated through fivefold cross-validation to avoid overfitting. We chose a classification threshold that targeted high sensitivity.

Results: After a mean follow-up of 7.1 years, 27 participants developed RA and 126 developed seropositive IA. The BRF demonstrated moderate predictive performance, characterised by high sensitivity (≥0.85) but modest specificity. Rheumatoid factors (RFs) had the highest importance in RA prediction, followed by symptoms of 'clinically suspected arthralgia' (CSA) scale. Age, gender and anti-RA33 autoantibodies were the main variables for the prediction of seropositive IA.

Conclusions: Overall, the results demonstrate that predicting RA by combining genetics, serological biomarkers, epidemiological risk factors and clinical signs is promising, although model generalisation remains challenging. The low prevalence of RA in the cohort complicates the development of highly accurate prediction models. Future efforts should focus on including external validation and potentially incorporating additional biomarkers to enhance the sensitivity and overall performance of the predictive tests.

Background and aim: Juvenile idiopathic arthritis-associated uveitis (JIAU) is a potentially blinding condition beginning in childhood. Flare-ups may occur throughout life, leading to cumulative ocular damage. This systematic review aimed to summarise the latest evidence on long-term ocular damage in adults with JIAU, focusing on studies published in the past 20 years.

Methods: The review protocol was registered in PROSPERO (ID 1033522). We included human studies on JIAU with at least 5 years of follow-up and/or young people ≥18 years old, published after 2000. Study quality was assessed using the Newcastle-Ottawa Scale. We extracted the cumulative incidence of complications and performed a meta-analysis to obtain pooled estimates (PE), assess heterogeneity, sensitivity, robustness and reporting bias using R packages.

Results: 22 retrospective or cohort studies were eligible, encompassing 2208 long-term JIAU cases. Study quality was rated as good in 10, fair in 7 and poor in 5. Despite high heterogeneity (p<0.01), sensitivity analyses supported robustness. Evidence of reporting bias was found for severe visual impairment and cataract. The pooled incidence of severe visual impairment was 16.6% (95% CI 9.9% to 22.6%) at approximately 18 years. Cataract was the most frequent complication (PE 44.3% (95% CI 27.5% to 61.7%)), followed by glaucoma, synechiae, band keratopathy and hypotony. In cohorts with >50% biologic exposure, PE were numerically lower.

Conclusion: Long-term prevalence and cumulative incidence of JIAU complications may persist in adulthood, with >10% developing severe visual impairment despite biologic therapy.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotising vasculitis characterised by tissue and blood hypereosinophilia. Cardiac involvement has previously been identified as the most significant predictor of mortality.

Objective: To identify and characterise previously untreated patients with EGPA and their cardiac manifestations at disease onset.

Methods: A retrospective monocentre study was conducted on 103 patients. Upon patient presentation, detailed multidisciplinary physical evaluations and laboratory diagnostics were performed. Cardiac events were defined as EGPA-related abnormalities in ECG, echocardiography, cardiac MRI, invasive coronary angiography or cardiac histopathology.

Results: Cardiac manifestations were diagnosed in 36 of 103 patients with EGPA (35%). Patients with EGPA with cardiac involvement (EGPA-CI) exhibited typical symptoms of EGPA concomitant with elevated cardiac biomarkers. Pericarditis (77%), cardiomyopathy with cardiac failure (55%) and definite myocarditis (36%) were the most common diagnoses, which in some cases resulted in cardiogenic shock (14%) or cardiac arrest (6%). Vasospastic coronary arteries causing myocardial infarctions were identified as a life-threatening cardiac manifestation in 8% of patients with EGPA-CI. Overall, patients with EGPA-CI presented with significantly higher disease activity and worse prognosis, with elevated median eosinophilic count and C-reactive protein levels.

Conclusions: Cardiac involvement is a common initial manifestation of EGPA and is associated with elevated systemic disease activity. In addition to pericarditis and myocarditis, coronary vasospasms were identified as a rare and severe manifestation of EGPA that may mimic myocardial infarction. Consequently, at the early stage of disease, patients may present with advanced cardiac impairment, emphasising the necessity of prompt diagnostic and therapeutic intervention to positively affect prognosis.

The management of rheumatoid arthritis (RA) has significantly improved, but a substantial number of patients still experience persistent disease activity, leading to the concept of 'difficult-to-treat RA' (D2T RA). The European Alliance of Associations for Rheumatology (EULAR) has provided a pivotal definition for D2T RA to unify clinical approaches and research methods. This definition frames D2T RA as an umbrella term for a diverse group of patients with management challenges stemming from various factors, including biological resistance, patient experience, and clinical complexities. This framework is invaluable for a previously ill-defined population, but its real-life application highlights areas for ongoing consideration and potential refinement. Here, we discuss some of the strengths and limitations of the EULAR definition for D2T RA.

Background: Pain and fatigue are among the most debilitating symptoms of systemic sclerosis (SSc), severely impairing quality of life (QoL). Pharmacological management is often inadequate, and evidence on exercise is limited. This study aimed to evaluate the effects of a tailored exercise programme on pain and fatigue in people with SSc (PwSSc).

Methods: This European multicentre randomised controlled trial (n=6) recruited 170 PwSSc (89% limited cutaneous SSc), randomised to an exercise intervention group (EIG) or usual care group (UCG). The EIG completed a 12-week, twice-weekly supervised programme combining 30 min of high-intensity interval training (HIIT) and 15 min of resistance training (RT), in addition to usual care. The UCG received usual care alone. Outcomes were assessed at baseline, 12 weeks (primary endpoint) and 24 weeks, with pain and fatigue as primary outcomes, and QoL, depression, functional ability, musculoskeletal strength/endurance and cardiorespiratory fitness as secondary outcomes.

Results: At 12 weeks, the mean group differences for the primary, fatigue (-10.4 (95% CI 19.4 to -1.4), p<0.05) and pain (0.48 (95% CI 0.21 to 0.76), p<0.05), secondary, depression (p<0.001), QoL and self-reported function (p<0.05) and exploratory outcomes musculoskeletal strength and endurance (p<0.01), and cardiorespiratory fitness (p<0.001) were significantly improved in EIG compared with UCG.

Conclusions: A 12-week supervised combined upper body exercise programme can improve pain, fatigue, depression, QoL, function, strength and cardiorespiratory fitness in PwSSc. HIIT combined with RT is safe for the study population and may serve as an effective non-pharmacological adjunct to pharmacotherapy to manage SSc symptoms and enhance QoL.

Trial registration number: NCT05234671.

Objectives: (1) To assess the risk of haematological malignancies in individuals with systemic sclerosis (SSc) compared with individuals without SSc; (2) to explore how the risk varies across groups stratified by sex and age; and (3) to determine when these malignancies present in relation to SSc diagnosis in a population-based setting.

Methods: We performed a nationwide cohort study using high-quality administrative healthcare registers covering virtually all Swedish residents. All individuals with SSc diagnosed during 2004-2019 and matched general population comparators were included. We identified all haematological malignancies in the study population using the Swedish Cancer Register and estimated the incidence rates using Poisson regression and the HRs using flexible parametric models. We stratified by sex and age and explored the incidence over time since SSc diagnosis.

Results: We observed 1720 individuals with incident SSc and 16 983 comparators for 11 480 and 131 021 person-years, respectively. Individuals with SSc had a higher risk of haematological malignancies compared with individuals without SSc (HR 2.2, 95% CI 1.4 to 3.1), especially B-cell malignancies (HR 3.0, 95% CI 1.7 to 4.8). The incidence rate and the HR were highest in men. The SSc over-representation of haematological malignancies was most evident in individuals aged 18-49 years at SSc diagnosis. Myeloid malignancies presented around SSc diagnosis (median 0.1 (IQR 8.2) years after SSc diagnosis) while lymphoid malignancies presented a few years later (median 3.1 (IQR 9.5)).

Conclusion: Individuals with SSc are afflicted by an increased risk of haematological malignancies, especially B-cell malignancies. The risk is highest in men. Myeloid malignancies tend to present closer to SSc diagnosis than lymphoid malignancies.